MRD for Myeloma- Pros and Cons

What is MRD for Myeloma? What are the pros and cons of measurable residual disease? First and foremost, let me say as a long-term MM survivor struggling with long-term and late-stage side effects, I am not as pro-MRD as the ChatGPT and Medscape summaries are below.

If there is one concept you take away from this blog post, let it be that while achieving a deep response to therapy, any therapy, is great, achieving a deep response is NOT required to live a long life with MM.

Meaning, don’t despair if you don’t reach MRD negativity. Plenty of MM survivors live long lives by managing their MM with tiny m-spikes or tiny amounts of MM in their marrow.

What is MRD? #myeloma

What are the pros and cons of measurable (formerly “minimal”) residual disease (MRD) for myeloma treatment?

Measurable (formerly “minimal”) residual disease (MRD) testing has become a critical tool in the management of multiple myeloma. It refers to the detection of small numbers of cancer cells that remain in the patient after treatment, which are undetectable using conventional methods like serum or urine protein electrophoresis.

Here are the key pros and cons of MRD testing in the treatment and monitoring of multiple myeloma:

✅ Pros of MRD Testing in Myeloma

1. Prognostic Power

MRD negativity is the strongest predictor of improved progression-free survival (PFS) and overall survival (OS), regardless of treatment regimen, cytogenetic risk, or disease stage.
It refines prognosis even in patients who are in complete response (CR) by conventional criteria.

2. Guides Treatment Intensity

Helps de-escalate treatment in MRD-negative patients to avoid unnecessary toxicity.
Conversely, can justify intensifying or maintaining therapy in MRD-positive patients who may appear to be in CR.

3. Improved Clinical Trial Endpoints

MRD is an FDA- and EMA-recognized surrogate endpoint in clinical trials, potentially shortening time to approval for new therapies.

4. Potential for Functional Cure

Sustained MRD negativity (especially at 10⁻⁶ sensitivity) is associated with long-term remission, raising the possibility of “operational cure” in some patients.

5. Predicts Early Relapse

MRD positivity can precede clinical relapse by months or years, allowing for early therapeutic intervention.

❌ Cons and Limitations of MRD Testing

1. Technical Complexity and Cost

Requires sensitive technologies like next-generation sequencing (NGS, e.g., clonoSEQ) or next-generation flow cytometry (NGF).
High cost, limited availability, and need for specialized lab infrastructure.

2. Bone Marrow Invasiveness

Most MRD assays are performed on bone marrow aspirates, which may not reflect extramedullary disease and are uncomfortable for patients.

3. Sampling Error

Myeloma often grows in patchy distributions. A single-site marrow sample may miss residual disease.
False negatives are possible if MRD cells are located outside the biopsy site or in extramedullary sites.

4. Uncertain Actionability

No universal standard of care yet for how to change treatment based on MRD results. For example, should MRD-positive patients receive more treatment even if in CR?

5. Lack of Integration into Guidelines

While widely studied and prognostic, MRD status is not yet uniformly integrated into frontline treatment guidelines (e.g., NCCN, ESMO) for adjusting therapy.

6. Not Always Predictive of Cure

Some MRD-negative patients still relapse, particularly in high-risk cytogenetic subgroups or those with aggressive disease biology.

Summary Table

Pros	Cons
Strong prognostic value	High cost and technical demands
Helps tailor therapy	Requires invasive bone marrow biopsy
Enables earlier relapse detection	Sampling and site variability
Facilitates clinical trial design	Uncertain impact on clinical decisions
May identify potential for functional cure	May miss extramedullary or focal disease

Final Thoughts

MRD testing is a powerful tool in myeloma management but is not yet a universal standard for guiding therapy changes. It’s best used in combination with other clinical factors and remains most valuable in research settings or specialized centers. As technology advances and cost drops, MRD may play a central role in personalized myeloma care.

Email me at David.PeopleBeatingCancer@gmail.com for information about managing your multiple myeloma.

Hang in there,

David Emerson

MM Survivor
MM Cancer Coach
Director PeopleBeatingCancer

MRD: A Shared Compass for Patients, Clinicians, and Regulators

The landscape of hematologic malignancies is shifting rapidly, in part due to the evolving significance of measurable (formerly “minimal”) residual disease (MRD). Once confined to the realm of research, MRD is emerging as a critical tool for clinical and regulatory decision-making. In conditions such as acute lymphoblastic leukemia(ALL), acute myeloid leukemia (AML), and multiple myeloma (MM), MRD has become more than a marker of the extent of disease burden; it now informs prognosis, therapeutic response, and access to novel treatments…

He clarified the distinction between activity and efficacy: activity refers to pharmacodynamic effects (eg, tumor shrinkage, MRD negativity), while efficacy denotes clinical benefit (eg, overall survival, progression-free survival). Activity-based endpoints such as MRD are already used in single-arm trials, particularly when randomized data are impractical. However, MRD should not replace overall survival as the final endpoint. “It can be used in conditional settings, provided final efficacy outcomes confirm its relevance,” he added…

MRD myeloma pros cons MRD myeloma pros cons MRD myeloma pros cons

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